Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by serologic and genetic factors and villous atrophy in the small intestine. Although some people test positive for antibodies and carry genetic alleles associated with celiac disease, they have relatively normal or slightly inflamed intestinal mucosa, with no or mild enteropathy. These patients are considered to have potential celiac disease (defined as increased serum levels of antibodies against tissue transglutaminase [tTG] without villous atrophy). They can have gastrointestinal and extra-intestinal symptoms or be completely asymptomatic.

It is not clear whether gluten-containing diets will lead to overt enteropathy over time, or whether these patients should be placed on a gluten-free diet.

To learn more about progression of potential celiac disease, Umberto Volta et al performed a prospective study to track clinical, serologic, and histologic features of 77 patients. The subjects had normal or slight inflammation of the small intestinal mucosa and were followed for 3 years.

Sixty-one patients had intestinal and extra-intestinal symptoms and 16 were completely asymptomatic at diagnosis. All subjects tested positive for IgA endomysial and tTG antibodies, except for 1 patient with IgA deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1.

Patients with symptoms were placed on a gluten-free diet and followed to assess their clinical and serologic features. Patients without symptoms were left on a gluten-containing diet and followed for 2 years with histologic evaluation.

Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients.

Of the 16 asymptomatic patients, who were left on the gluten-containing diets, only 1 developed mucosal flattening; levels of anti-endomysial and tTG antibodies fluctuated in 5 of these patients or became undetectable.

Volta et al recommend using caution in placing asymptomatic patients on gluten-free diets, based on the spontaneous loss and fluctuations in serologic markers of celiac disease while they are on gluten-containing diets. They recommend gluten-free diets for symptomatic adults, but say that asymptomatic patients should continue their gluten-containing diets under strict clinical, serologic, and histologic surveillance. They believed that only a small proportion of asymptomatic adults will develop active disease over time.

In an editorial that accompanies the article, Jocelyn A. Silvester and Ciarán P. Kelly point out that the asymptomatic patients were generally younger (median 21 years vs 36 years for those who were symptomatic), so symptomatic celiac disease might develop with more time.

Silvester and Kelly say the findings of Volta et al are consistent with this guideline, in that symptomatic patients were HLA DQ2- or HLA DQ8-positive and responded to a gluten-free diet, even if they did not have villous atrophy. Biopsy findings were therefore not required for management and did not seem to predict response to the gluten-free diet. The findings suggest that a gluten-free diet is worth trying in symptomatic patients with potential celiac disease.

2 Comments

Umberto VoltaApril 29, 2016

Potential celiac disease (PCD) is an emerging clinical condition in the spectrum of gluten sensitive enteropathy. The spread of serological screening by means of tissue transglutaminase and endomysial antibodies has contributed to increase the number of PCD diagnoses in latest years. While the diagnostic criteria of PCD have long been known, the dietary management of this condition remained to be defined so far. Our study ( Volta et al, Clin Gastroenterol Hepatol 2016) fills this gap clearly establishing that only PCD patients with symptoms benefit from a gluten-free diet, whereas asymptomatic patients should be left on a gluten-containing diet with a close clinical, serological and histological follow-up. In this respect, the evaluation of gluten-related symptoms made by an expert physician is crucial for identifying patients to treat. Among the overlooked gluten-related signs, our study shows that the poor outcome of pregnancy should be definitely taken into consideration since the gluten-free diet in women with recurrent miscarriages allows them to carry pregnancies to term.

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About the Author

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology. She has worked as an editor at biomedical research journals and as a science writer for 15 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.